Researchers at Cleveland Clinic have developed a new tool called CRC-PRO that allows physicians to quickly and accurately predict an individual's risk of colorectal cancer, as published in an open-access article in the January-February 2014 issue of the Journal of the American Board of Family Medicine. CRC-PRO, or Colorectal Cancer Predicted Risk Online, is designed to help both patients and physicians determine when screening for colorectal cancer is appropriate. Current guidelines recommend patients are screened at the age of 50. However, with this new tool, physicians will be better able to identify who is truly at risk and when screenings for patients are necessary. To develop the calculator, the researchers – led by Brian Wells, M.D., Ph.D., of the Department of Quantitative Health Sciences in Cleveland Clinic's Lerner Research Institute – analyzed data on over 180,000 patients from a longitudinal study conducted at the University of Hawaii. Patients were followed for up to 11.5 years to determine which factors were highly associated with the development of colorectal cancer. "Creating a risk calculator that includes multiple risk factors offers clinicians a means to more accurately predict risk than the simple age-based cutoffs currently used in clinical practice," said Dr. Wells. "Clinicians could decide to screen high-risk patients earlier than age 50, while delaying or foregoing screening in low-risk individuals." Dr. Wells and his colleagues hope that their new, user-friendly calculator will help improve the efficiency of colorectal cancer screenings. They also believe prediction tools like this can help lower healthcare costs by cutting down on unnecessary testing. The Multiethnic Cohort Study comprised a diverse ethnic population.

Scientists have found a genomic deletion that affects fertility and milk yield in dairy cattle at the same time. The discovery can help explain a dilemma in dairy cattle breeding: the negative correlation between fertility and milk production. The work was published online on January 2, 2014 in the open-access journal PLOS GENETICS. For the past many years, milk yield in Scandinavian dairy cattle has gone in one clear direction: up. This has been due to targeted breeding programs and modern breeding methods. Despite putting large weight on the breeding goal in Nordic countries, almost no improvement is achieved for fertility. It now seems that this unfavourable correlation between milk yield and fertility is partially affected by a deletion of a simple gene sequence. The presence and effects of this mutation have recently been discovered by scientists from Aarhus University, the University of Liège, and MTT Agrifood Research Finland, in collaboration with the Danish Agricultural Advisory Service and the Nordic Cattle Genetic Evaluation. Scientists, farmers, and advisors have generally assumed that the reduction in fertility is primarily due to the negative energy balance of high-producing cows at the peak of their lactation, but now the scientists have also found a genetic explanation. “We have discovered a deletion encompassing four genes as the causative variant and shown that the deletion is a recessive embryonically lethal mutation,” explains Dr. Goutam Sahana. This means that the calves die while they are still embryos and are aborted or reported as insemination failure. The fact that the mutation is recessive means that both parents must carry it and pass the genes on to their calf for the calf to be affected.

Researchers analyzed the body orientation of 70 dogs of different breeds, while the dogs relieved themselves in the open country and without being on the leash. The statistical analyses of the more than 7,000 observations (recorded together with the currently prevailing environmental conditions of the location, time of day, and other important parameters such as the familiarity of the terrain for each dog) was frustrating. In contrast to grazing cows, hunting foxes, and landing waterfowl (previous studies of the research collective), the dogs showed no clear preference for a particular body alignment while doing number one or number two. But then the researchers around Dr. Vlastimil Hart and Prof. Dr. Hynek Burda made a striking discovery. They sorted the collected data according to the small variations of the geomagnetic field during the period of data collection. These irregular, tiny changes in the intensity and declination of the magnetic field lines are recorded by magnetic observatories and freely accessible online. The emerging picture of the analysis of the categorized data is as clear as it is astounding: dogs prefer a body-alignment along the magnetic north-south axis, but only during periods of calm magnetic field conditions. After taking into account all other factors, the researchers concluded that with this discovery they provide clear indication of a magnetic sense in our four-legged friends. To many dog owners who know about the good navigation abilities of their protégés, the findings might not come as a surprise – but rather as an explanation for the "supernatural" abilities, although it is not clear to the researchers what the dogs might use their magnetic sense for.

Stretches of DNA called retrotransposons, often dubbed “junk DNA,” might play an important role in schizophrenia. In a study published online on January 2, 2013 in the journal Neuron, a Japanese team revealed that LINE-1 retrotransposons are abnormally abundant in the schizophrenia brain, modify the expression of genes related to schizophrenia during brain development, and may be one of the causes of schizophrenia. Retrotransposons are short sequences of DNA that autonomously amplify and move around the genome. One class of retrotransposons named Long Interspersed Nuclear Elements (LINEs) make up a large part of the eukaryotic genome and it is believed that they may contribute to a number of disorders and diseases, such as cancer. LINE-1 retrotranspons have been shown to be more abundant in brain cells than in other cells in the body in adults, providing evidence for enhanced activity of LINE-1s in the human brain. However, the role played by LINE-1s in mental disorders, and in particular schizophrenia, has remained unclear. The team led by Dr. Kazuya Iwamoto from the University of Tokyo and Dr. Tadafumi Kato from the RIKEN Brain Science Institute demonstrated that the number of LINE-1 copies is elevated in the post-mortem brains of patients with schizophrenia. They show, using mouse and macaque models for schizophrenia and induced pluripotent stem (iPS) cells, that exposure to environmental risk factors during development, as well as the presence of genetic risk factors for schizophrenia, can lead to increased levels of LINE-1 copies in neurons. Employing whole genome analysis, the authors reveal that in schizophrenia patients LINE-1 reinserts into genes involved in synaptic function or schizophrenia and may result in disruptions in their normal functions.

Scientists from The Scripps Research Institute (TRSI) have revealed an atomic-level view of a genetic defect that causes a form of muscular dystrophy, myotonic dystrophy type 2, and have used this information to design drug candidates with potential to counter those defects—and reverse the disease. “This the first time the structure of the RNA defect that causes this disease has been determined,” said TSRI Associate Professor Matthew Disney, who led the study. “Based on these results, we designed compounds that, even in small amounts, significantly improve disease-associated defects in treated cells.” Myotonic dystrophy type 2 is a relatively rare form of muscular dystrophy that is somewhat milder than myotonic dystrophy type 1, the most common adult-onset form of the disease. Both types of myotonic dystrophy are inherited disorders that involve progressive muscle wasting and weakness, and both are caused by a type of genetic defect known as an “RNA repeat expansion,” a series of nucleotides repeated more times than normal in an individual’s genetic code. The repeat binds to the protein MBNL1, rendering it inactive and resulting in RNA splicing abnormalities—which lead to the disease. Many other researchers had tried to find the atomic-level structure of the myotonic dystrophy 2 repeat, but had run into technical difficulties. In a technique called X-ray crystallography, which is used to find detailed structural information, scientists manipulate a molecule so that a crystal forms. This crystal is then placed in a beam of X-rays, which diffract when they strike the atoms in the crystal. Based on the pattern of diffraction, scientists can then reconstruct the shape of the original molecule.